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Open Access Publications from the University of California

Scholarly Works (26 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2015)

Syphilis is a curable disease, yet 10 million persons worldwide are infected each year, of which 1.4 million are pregnant women. Syphilis is an infection caused by the spirochete Treponema pallidum and frequently has atypical presentations that may be difficult to differentiate from other sexually transmitted infections (STIs) making effective diagnostics essential to the identification of infection. Additionally, the manifestations of the disease vary depending on the duration of infection and time of presentation. There are four stages-primary, secondary, latent (early and late), and tertiary.

Syphilis screening and treatment programs that utilize laboratory-based testing have been hampered by limited laboratory access, long turn-around time for results, and loss to follow-up of syphilis infected individuals. When syphilis diagnostic testing involves multiple tests performed off-site, only a proportion of infected individuals receive treatment and continued transmission occurs.

A rapid test is a simple point-of-care test that can be used in a variety of settings and provides a result to guide clinical management during the time of the initial consultation (ideally within 30 minutes or less). The advent of rapid point-of-care tests for syphilis has reduced barriers and allowed for new health systems approaches to syphilis prevention, including same day testing and treatment. Dual rapid tests that have multiple analytes for the detection of antibodies for both HIV and syphilis infections are now available.

Our first study addressed preferences for dual HIV/syphilis tests through a conjoint survey analysis. Conjoint analysis is a method for systematically estimating consumer preferences across discrete attributes. Conjoint analysis has been used extensively in marketing research and measures the value that consumers place on each feature of a product. Conjoint analysis has recently begun to be applied in health research. We recruited 298 men and women 18 years of age and over seeking testing or care at GHESKIO (Haitian Study Group for Kaposi’s sarcoma and Opportunistic Infections) clinics. We created 8 hypothetical dual test profiles varying across six dichotomous attributes: cost (free versus $4), accuracy (no false positive versus false positive), time-to-result (20 minutes versus 1 week), blood draw method (finger prick versus venipuncture), number of draws (1 versus 2), and test type (rapid versus laboratory). Cost (free vs. $4; impact score=27.2, SD=36.6, p<.0001) had the highest impact on likelihood of testing, followed by number of blood draws (1 versus 2; impact score=17.5, SD=29.8, p<.0001), blood draw method (fingerprick versus venipuncture; impact score=9.7, SD=26.5, p<.0001), test type (rapid versus laboratory; impact score= -4.5, SD=21.9 , P=.0005), and time-to-result (20 minutes versus 1 week; impact score=3.6, SD=25.6, p=.0139). This analysis showed that implementation of a low cost dual rapid test in the laboratory for HIV and syphilis could be used to improve screening uptake and accessibility to accelerate time to treatment.

Our second study was a field study of a dual HIV and syphilis rapid test in Port-au-Prince, Haiti. Field studies using whole blood fingerprick specimens are essential to understand how the test will perform in real-world settings. We found that for the HIV test component, sensitivity and specificity were 99.2% (95% CI: 95.8%, 100%) and 97.0% (95% CI: 93.2%, 99.0%), respectively; and for the syphilis component were 96.5% (95% CI: 91.2%, 99.0%) and 90.8% (95% CI: 85.7%, 94.6%), respectively. This test performed well and could be considered for wider use to increase rates of HIV and syphilis screening.

Our final analysis was an epidemiological bias analysis using estimates of potential misclassification by use of an imperfect gold standard test. We used regression calibration methods to assess the effect of reference standard misclassification bias using the syphilis component of the dual HIV and syphilis rapid test as an example. We concluded by making recommendations for reporting diagnostic performance ranges instead of point estimates when using an imperfect reference test.

In conclusion, dual HIV and syphilis testing is a preferred screening modality that can be used to streamline HIV and syphilis prevention and case finding. These tests perform well in both laboratory and point-of-care settings and should be considered for wider implementation. Use of regression calibration methodology can provide accurate information on the potential performance characteristics of these tests when a perfect gold standard test is unavailable.

    Cover page: Contributions to the improvement and understanding of new diagnostics for HIV infection and syphilis
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2021)

    Abstract

    Associations between substance use disorders and outbreaks of HIV and acute viral hepatitis have received considerable attention, but less research has focused on links between substance use disorders and sexually transmitted infections, apart from alcohol misuse. This narrative review describes the history of this public health crisis in the United States and direct and indirect effects opioids and specific stimulants have on high-risk sexual behaviors. We also review the epidemiology of sexually transmitted infections associated with opioids and stimulants in the United States and discuss opportunities for integrated interventions.
      Cover page: Collateral Damage: A Narrative Review on Epidemics of Substance Use Disorders and Their Relationships to Sexually Transmitted Infections in the United States
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2019)
      Background Most studies evaluating extragenital testing performance for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) detection by the Xpert® CT/NG show high per cent agreement with comparison assays; however, the precision around positive per cent agreement is low and thus the values that have been reported are not highly informative. Therefore, a systematic review was conducted and data from five studies were combined to better assess positive per cent agreement.

      Methods

      The literature indexed on PubMed.gov was searched. Included studies were those that were an evaluation of the Xpert CT/NG assay with rectal and/or pharyngeal specimen types compared with another nucleic acid amplification test (NAAT), the Aptima transcription mediated amplification assay. A full Bayesian method was used for bivariate fixed-effect meta-analysis of positive and negative per cent agreement and pooled estimates (and 95% confidence intervals (CI)) were presented for each.

      Results

      The pooled positive and negative per cent agreement for detection of CT in rectal specimens was 89.72% (95% CI: 84.97%, 93.64%) and 99.23% (95% CI: 98.74%, 99.60%), and in pharyngeal specimens, they were 89.96% (95% CI: 66.38%, 99.72%) and 99.62% (95% CI: 98.95%, 99.95%) respectively. For NG detection in rectal specimens, the pooled positive and negative per cent agreement was 92.75% (95% CI: 87.91%, 96.46%) and 99.75% (95% CI: 99.46%, 99.93%), and in pharyngeal specimens, they were 92.51% (95% CI: 85.84%, 97.18%) and 98.56% (95% CI: 97.69%, 99.23%) respectively.

      Conclusions

      It was found that the Xpert CT/NG assay performed similarly to the Aptima transcription mediated amplification assay for the detection of CT and NG in extragenital specimens. The Xpert assay has the benefit of providing faster results at the point-of-care, thus reducing the turnaround time for results, potentially enabling same-day treatment.
        Cover page: Meta-analysis of the Cepheid Xpert® CT/NG assay for extragenital detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2022)
        Recovery of Neisseria gonorrhoeae isolates exposed to a range of transport times and temperatures was quantitatively assessed for two transport devices, BioMed Diagnostics' InTray GC® and Copan Diagnostics' Liquid Amies Elution Swab (ESwab®) Collection and Transport System. Respective devices were inoculated with N. gonorrhoeae, exposed to simulated transport conditions and spread-plated from serial dilutions in duplicates onto chocolate agar in order to count CFU (colony-forming units) in the range of 25-250. Baseline CFU/mL averages of time-zero transport for each device was compared to either 24 hour (Eswab) or 72 hour (InTray GC) CFU/mL average to assess recovery of six clinical isolates of N. gonorrhoeae, and differences showing no greater than a 3 log10 (± 10%) decline between comparative time points qualified as acceptable. Our findings suggest that the InTray GC system has the potential to transport clinical isolates for ≤72 hours with acceptable N. gonorrhoeae recovery.
          Cover page: 72-Hour transport recovery of antimicrobial resistant Neisseria gonorrhoeae isolates using the InTray® GC method
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2019)
          Background Most studies evaluating extragenital testing performance for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) detection by the Xpert® CT/NG show high per cent agreement with comparison assays; however, the precision around positive per cent agreement is low and thus the values that have been reported are not highly informative. Therefore, a systematic review was conducted and data from five studies were combined to better assess positive per cent agreement.

          Methods

          The literature indexed on PubMed.gov was searched. Included studies were those that were an evaluation of the Xpert CT/NG assay with rectal and/or pharyngeal specimen types compared with another nucleic acid amplification test (NAAT), the Aptima transcription mediated amplification assay. A full Bayesian method was used for bivariate fixed-effect meta-analysis of positive and negative per cent agreement and pooled estimates (and 95% confidence intervals (CI)) were presented for each.

          Results

          The pooled positive and negative per cent agreement for detection of CT in rectal specimens was 89.72% (95% CI: 84.97%, 93.64%) and 99.23% (95% CI: 98.74%, 99.60%), and in pharyngeal specimens, they were 89.96% (95% CI: 66.38%, 99.72%) and 99.62% (95% CI: 98.95%, 99.95%) respectively. For NG detection in rectal specimens, the pooled positive and negative per cent agreement was 92.75% (95% CI: 87.91%, 96.46%) and 99.75% (95% CI: 99.46%, 99.93%), and in pharyngeal specimens, they were 92.51% (95% CI: 85.84%, 97.18%) and 98.56% (95% CI: 97.69%, 99.23%) respectively.

          Conclusions

          It was found that the Xpert CT/NG assay performed similarly to the Aptima transcription mediated amplification assay for the detection of CT and NG in extragenital specimens. The Xpert assay has the benefit of providing faster results at the point-of-care, thus reducing the turnaround time for results, potentially enabling same-day treatment.
            Cover page: Meta-analysis of the Cepheid Xpert<sup>®</sup> CT/NG assay for extragenital detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections.
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2021)

            Background

            Pooled testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may be a cost-saving solution to increase screening by simplifying testing procedures and reducing resource burdens. We conducted a systematic review and meta-analysis to examine the performance of pooled 3-anatomic-site testing (pharyngeal, rectal, and urogenital sites) for CT and NG in comparison with single-anatomic-site testing.

            Methods

            We conducted a systematic literature search in PubMed, Embase, and Web of Science to identify original evaluation studies of the performance of pooled testing for CT and NG infections and identified 14 studies for inclusion. Each study was systematically evaluated for bias. We conducted bivariate fixed-effects and random-effects meta-analyses using a full Bayesian method of the positive percent agreement and negative percent agreement.

            Results

            The combined positive percent agreement for CT was 93.11% (95% confidence interval [CI], 91.51%-94.55%), and the negative percent agreement was 99.44% (95% CI, 99.18%-99.65%). For NG, the combined positive percent agreement was 93.80% (95% CI, 90.26%-96.61%), and the negative percent agreement was 99.73% (95% CI, 99.30%-99.97%).

            Conclusions

            We found that pooled 3-anatomic-site tests performed similarly to single-anatomic-site tests for the detection of CT and NG. The pooled 3-anatomic-site tests have the added potential benefit of reduced cost and resource requirement, which could lead to improved testing access and screening uptake.
              Cover page: Pooled 3-Anatomic-Site Testing for Chlamydia trachomatis and Neisseria gonorrhoeae: A Systematic Review and Meta-Analysis
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2013)
              Abstract Background The optimal treatment of early syphilis (primary, secondary and early latent) in HIV-infected patients remains controversial. The Center for Diseases Control STD Treatment Guidelines recommended 1 dose of benzathine penicillin G (BPG) regardless of HIV infection. However, many providers modify the treatment for early syphilis. Methods We performed a retrospective chart review of all cases of early syphilis with positive serologic test results in HIV-infected patients from May 2006 to May 2011 in 2 large, urban HIV clinics. Early syphilis includes primary, secondary, and early latent syphilis. Serological failure was defined as a lack of 4-fold decrease in rapid plasma reagent (RPR) titers 9 to 12 months after syphilis treatment. Patients whose RPR titers decreased after treatment and subsequently increased 4-fold at 9 to 12 months were excluded from the analysis of serological response because of possibility as “reinfection”. Baseline characteristics were tested as predictive factors of serological failure using a univariate and multivariate logistic regression model, respectively. Results Of 560 patients with confirmed cases of early syphilis, 51 (9.0%) experienced serological failure. Multivariate logistic regression modeling demonstrated that the predictive factors associated with serological failure after early syphilis treatment were baseline RPR titer ≤ 1:16 (OR 3.91 [95% CI, 2.04-7.47]), a previous history of syphilis (OR 3.12 [95% CI, 1.55-6.26]), and a CD4 T-cell count below 350 cells/ml (OR 2.41 [95% CI, 1.27-4.56]). Of note, type of syphilis treatment (1 dose versus 3 doses of BPG) did not appear to affect the proportion of serological failure (4% versus 10%, P = 0.29), however the power of this study to detect small differences was limited. Conclusions HIV-infected patients with baseline RPR titer ≤1:16, syphilis history, and/or a CD4 T-cell count <350 cells/ml should be closely monitored for serologic failure after early syphilis treatment. This study did not detect a substantial difference between treatment with > 1 dose of BPG and decreased frequency of serological failure, supporting the current recommendation that one dose of BPG is adequate treatment for early syphilis in HIV-infected patients.
                Cover page: Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging Era of universal antiretroviral therapy use
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2021)

                Background

                Although molecular testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) is highly sensitive, the cost can be prohibitive. Those high costs are amplified when the recommended screening approach is used, which requires separate testing of specimens from 3 anatomic sites (rectal, pharyngeal and urogenital). Although individual molecular testing is standard of care, pooled testing may offer a cost-saving alternative.

                Methods

                Using the Xpert® CT/NG assay (Cepheid, Sunnyvale, CA) we tested urine, rectal and pharyngeal swabs for CT and NG in a high-risk cohort of participants assigned male at birth who reported sex with other persons who were assigned male at birth. Remnant specimens (0.34 mL from each anatomic site) were combined to perform a single 'pooled' test. We calculated positive and negative percent agreement between the pooled testing results with standard of care Xpert CT/NG test results as the reference.

                Results

                We conducted 644 pooled tests. Of those, 598 (92.3%) gave CT and NG results. The CT-positive and -negative percent agreement were 90.1% (95% confidence interval [CI], 80.7-95.9%) and 99.2% (98.1-99.8%), respectively. The NG-positive and -negative percent agreement were 96.2% (95% CI, 86.8-99.5%) and 99.8% (95% CI, 99.0-100%), respectively. Pooled testing identified 4 CT and 1 NG infections that were negative at all anatomic sites by individual testing.

                Conclusions

                Three-site pooled CT and NG testing performs similarly to single anatomic site testing among tests providing a valid result. Future cost analyses should evaluate the cost effectiveness of pooled 3-site testing to determine if such a strategy improves the feasibility and accessibility of molecular sexually transmitted infection testing.
                  Cover page: The Performance of Pooled 3 Anatomic Site Testing for Chlamydia trachomatis and Neisseria gonorrhoeae Among Men Who Have Sex With Men and Transgender Women
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2016)

                  Background

                  Dual rapid tests for HIV and syphilis infections allow for detection of HIV infection and syphilis at the point-of-care. Those tests have been evaluated in laboratory settings and show excellent performance but have not been evaluated in the field. We evaluated the field performance of the SD BIOLINE HIV/Syphilis Duo test in Port-au-Prince, Haiti using whole blood fingerprick specimens.

                  Methods

                  GHESKIO (Haitian Study Group for Kaposi's Sarcoma and Opportunistic Infections) clinic attendees 18 years of age or older were invited to participate. Venipuncture blood specimens were used for reference testing with standard commercially available tests for HIV and syphilis in Haiti. The sensitivity and specificity of the Duo test compared to the reference standard were calculated. The exact binomial method was used to determine 95 % confidence intervals (CI).

                  Results

                  Of 298 study participants, 237 (79.5 %) were female, of which 49 (20.7 %) were pregnant. For the HIV test component, the sensitivity and specificity were 99.2 % (95 % CI: 95.8 %, 100 %) and 97.0 % (95 % CI: 93.2 %, 99.0 %), respectively; and for the syphilis component were 96.5 % (95 % CI: 91.2 %, 99.0 %) and 90.8 % (95 % CI: 85.7 %, 94.6 %), respectively. In pregnant women, the sensitivity and specificity of the HIV test component were 93.3 % (95 % CI: 68.0 %, 99.8 %) and 94.1 % (95 % CI: 80.3 %, 99.3 %), respectively; and for the syphilis component were 100 % (95 % CI:81.5 %, 100 %) and 96.8 % (95 % CI:83.3 %, 99.9 %), respectively.

                  Conclusion

                  The Standard Diagnostics BIOLINE HIV/Syphilis Duo dual test performed well in a field setting in Haiti and should be considered for wider use.
                    Cover page: Dual rapid lateral flow immunoassay fingerstick wholeblood testing for syphilis and HIV infections is acceptable and accurate, Port-au-Prince, HaitiCreative Commons 'BY-NC-SA' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2017)
                    Introduction Syphilis and HIV screening is highly recommended for pregnant women and those at risk for infection. We used conjoint analysis to identify factors associated with testing preferences for HIV and syphilis infection. Methods We recruited 298 men and women 18 years and over seeking testing or care at GHESKIO (Haitian Study Group for Kaposi's Sarcoma and Opportunistic Infections) clinics. We created eight hypothetical dual HIV-syphilis test profiles varying across six dichotomous attributes. Participants were asked to rate each profile using Likert preference scales. An impact score was generated for each attribute by taking the difference between the preference scores for the preferred and non-preferred level of each attribute. Two-sided one-sample t-test was used to generate p values. Results Of 298 study participants, 61 (20.5%) were male. Of 237 females, 49 (20.7%) were pregnant. Cost (free vs. US$4; p < .0001) had the highest impact on willingness to test, followed by number of blood draws (1 vs. 2; p < .0001), blood draw method (fingerprick vs. venipuncture; p < .0001), test type (rapid vs. laboratory; p = .0005), and time-to-result (20 minutes vs. 1 week; p = .0139). Conclusion HIV and syphilis testing preferences for this study sample in Port-au-Prince prioritized cost, single fingerprick, laboratory-based testing and timeliness.
                      Cover page: Attributes of diagnostic tests to increase uptake of dual testing for syphilis and HIV in Port-au-Prince, HaitiCreative Commons 'BY-NC-SA' version 4.0 license
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